Frailty: Scaling from Cellular Deficit Accumulation?

Abstract

Cells age in association with deficit accumulation via mechanisms that are far from fully defined. Even so, how deficits might scale up from the subcellular level to give rise to clinically evident age-related changes can be investigated. This 'scaling problem' can be viewed either as a series of little-related events that reflect discrete processes--such as the development of particular diseases--or as a stochastic process with orderly progression at the systems level, regardless of which diseases are present. Some recent evidence favors the latter hypothesis, but determining the best approach to study how deficits scale remains a key goal for understanding aging. In consequence, approaching the problem of frailty as one of the scaling of subcellular deficits has implications for understanding aging. Considering the cumulative effects of many small deficits appears to allow for the observation of important aspects of the behavior of systems that are close to failure. Mathematical modeling offers useful possibilities in clarifying the extent to which different clinical scales measure different phenomena. Even so, to be useful, mathematical modelling must be clinically coherent in addition to mathematically sound. In this regard, queuing appears to offer some potential for investigating how deficits originate and accumulate.